Abstract
BackgroundThe aim of this study was to develop the near infrared fluorescence (NIRF)-based imaging agent for the visualization of vascular endothelial growth factor (VEGF) in colon cancer. AlexaFluor 750 conjugating with bevacizumab, and injected intravenously into nude mice bearing VEGF over-expressing HT29 human colorectal cancer. Optical imaging was performed at 15 min, 24 h and 48 h post injection. Immunofluorescences staining of the tumor sections were performed. HT29 colorectal cancer xenografts were clearly visualized with bevacizumab-AlexaFluor 750.ResultsEx vivo analysis showed 2.1 ± 0.4%, 37.6 ± 6.3% and 38.5 ± 6.2% injected dose/g accumulated in the tumors at 15 min, 24 h and 48 h respectively. Tumor uptake was significantly decreased in pretreated with excess of bevacizumab (p = 0.002). Immunofluorescence analysis showed strong staining of anti-CD 31 antibody around the blood vessels. Anti-VEGF-A and bevacizumab showed heterogeneous expression throughout the tumor.ConclusionsCurrent study successfully detected the VEGF expression in HT29 colorectal cancer xenografts, signifying as a potential agent for non-invasive imaging of VEGF expression, which may be applied in clinical practice.
Highlights
The aim of this study was to develop the near infrared fluorescence (NIRF)-based imaging agent for the visualization of vascular endothelial growth factor (VEGF) in colon cancer
Bevacizumab was labeled with NIRF agent, and the optical imaging and biodistribution of the conjugate were investigated in nude mice bearing VEGF overexpressing HT29 colorectal cancer xenografts
The absorption and fluorescence emission characteristics of the bevacizumab-AlexaFluor 750 was found to be similar to those of free AlexaFluor 750, as apparent from the spectra measured in PBS, suggesting that the fluorescence property of the AlexaFluor 750 was not affected by the conjugation to the bevacizumab
Summary
The aim of this study was to develop the near infrared fluorescence (NIRF)-based imaging agent for the visualization of vascular endothelial growth factor (VEGF) in colon cancer. Optical imaging is an emerging modality of choice for preclinical studies to evaluate the expression of different kinds of proteins. It allows visualization of subcellular structures on a microscopic scale, as well as macroscopic distribution of fluorescent labels in vivo in small animals [7]. The present study evaluated the feasibility of using NIRF-labeled bevacizumab for tumor imaging in colon cancer xenografts. Bevacizumab was labeled with NIRF agent, and the optical imaging and biodistribution of the conjugate were investigated in nude mice bearing VEGF overexpressing HT29 colorectal cancer xenografts
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